Daily azithromycin for one year decreased chronic obstructive pulmonary disease exacerbations and improved quality of life among select patients, researchers reported. More...

Test yourself

MKSAP Quiz: swelling of the feet and legs in untreated HIV infection

This week's quiz asks readers to evaluate a young man with untreated HIV infection and swelling of the feet and legs. More...

Hypertension

Ambulatory blood pressure monitoring may be most cost-effective for hypertension diagnosis

Ambulatory measurement is the most cost-effective method of diagnosing high blood pressure, a new analysis concluded. More...

Asleep blood pressure could present a novel target for CVD risk

Taking one or more blood pressure drugs at bedtime reduced asleep blood pressure and cardiovascular disease risk compared to taking all hypertension drugs upon awakening, a new study found. More...

Prescribing

Long-term medications often discontinued during hospitalization

Patients taking medication for chronic diseases risk those prescriptions being discontinued when they are hospitalized, especially if they are admitted to an intensive care unit, a new study found. More...

FDA update

Daily citalopram dose shouldn't be higher than 40 mg

The antidepressant citalopram hydrobromide (Celexa) should no longer be used at doses greater than 40 mg/d, according to a new warning from the FDA. More...

CMS update

Applications now being accepted for bundled payment initiative

The Centers for Medicare and Medicaid Services is currently soliciting applications for the Bundled Payments for Care Improvement Initiative. More...

Education

Correctional health care conference to be held in October

The National Commission on Correctional Health Care will hold its national conference Oct. 15-19, 2011, in Baltimore. More...

Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for our new cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service. More...

Editor's note: ACP InternistWeekly will not be published next week due to the Labor Day holiday.

Highlights

Primary care physicians' adoption of opioid risk reduction strategies is limited, even in treatment of patients at increased risk of misuse, a new study has found.

Researchers conducted a retrospective cohort study using data from eight primary care practices sharing an electronic health record within the University of Pennsylvania Health System from January 2004 to April 2008. Patients were 18 years of age and older, had three or more visits, needed three or more opioid prescriptions at least 21 days apart within 6 months, and had chronic, non-cancer pain. Of 1,612 patients, most were female, black, and resided in ZIP codes where median household income was below $35,000 per year.

Researchers studied three risk reduction strategies and five risk factors for opioid misuse. The risk reduction strategies included any urine drug test, regular office visits at least once every 6 months and within 30 days of modifying opioid treatment, and restricted early refills of one or fewer opioid prescriptions more than a week early. Risk factors for opioid misuse included age younger than 45 years, drug or alcohol use disorder, tobacco use, or mental health disorder. Results appeared in the September Journal of General Internal Medicine.

The mean duration of observed opioid treatment was 1.9 years, and 54.5% of the cohort was treated for at least 18 months. During this time, patients received a mean of 20.2 opioid prescriptions. Within the study cohort, 8.0% had at least one urine drug test, 49.8% had regular office visits, and 76.6% had restricted early refills. Overall, 44 (2.7%) of the cohort received all three risk reduction strategies. Prevalence of risk factors for opioid misuse was 29.1% for age younger than 45 years, 7.6% for drug use disorder, 4.5% for alcohol use disorder, 16.1% for tobacco use, and 48.4% for mental health disorder.

The authors wrote, "Overall, our findings reveal disturbingly low use of monitoring strategies to reduce the risk of adverse events from long-term opioid treatment and indicate that primary care physicians are not employing all these approaches more intensively for patients at increased risk of misuse."

Although patients at increased risk of opioid misuse were more likely to undergo urine tests, less than one-quarter of patients with three or more risk factors had any urine drug test. Patients at increased risk of opioid misuse were more likely to receive more than one early refill, and their office-based monitoring was no greater than for persons with no risk factors. "This lack of face-to-face encounters represents missed opportunities for physicians to examine responses to treatment, propose alternative treatments when response is inadequate, detect side effects, and assess for misuse," the authors wrote.

Editorialists commented, "The increasing prevalence of misuse of and addiction to prescription opioid analgesics attributable to physician prescription appears to be the result of a perfect storm: inconsistent and inadequate physician education, lack of sufficient evidence of efficacy and safety of opioid analgesia for chronic pain, and lack of adherence to guideline-based risk assessment and monitoring."

A systemic approach included monitoring all patients, basing intensity on risk factors. Primary care clinicians should collaborate with clinicians in behavioral health, pharmacists and addiction specialists when misuse occurs. Finally, patients must be better educated on the risks and their mitigation strategies, the authors said.

Daily azithromycin for one year decreased chronic obstructive pulmonary disease (COPD) exacerbations and improved quality of life among select patients, researchers reported.

Researchers conducted a prospective, parallel-group, placebo-controlled trial of 1,142 patients age 40 years and older. Participants from 17 sites associated with 12 academic U.S. health centers were randomized to receive 250 mg of oral azithromycin or placebo daily. The study was supported by grants from the National Heart, Lung, and Blood Institute. Results appeared in the Aug. 25 issue New England Journal of Medicine.

Studied patients had a clinical diagnosis of COPD (defined as a smoking history of at least 10 pack-years, a ratio of postbronchodilator forced expiratory volume in 1 second [FEV1] to forced vital capacity of <70%, and a postbronchodilator FEV1 of <80% of the predicted value), were using continuous supplemental oxygen or had received systemic glucocorticoids within the previous year, had gone to an emergency department or had been hospitalized for an acute exacerbation of COPD, and had not had an acute exacerbation of COPD for at least four weeks before enrollment.

Exclusion criteria were asthma, a resting heart rate greater than 100 beats per minute, a prolonged corrected QT (QTc) interval greater than 450 ms, use of medications that prolong the QTc interval or are associated with torsades de pointes (with the exception of amiodarone), and an existing hearing impairment.

The primary outcome was the time to the first acute COPD exacerbation. A total of 1,641 acute COPD exacerbations occurred, 741 among the 558 azithromycin patients and 900 among the 559 placebo patients. The rates of acute COPD exacerbations per patient-year were 1.48 and 1.83, respectively (P=0.01; rate ratio from negative binomial analysis, 0.83; 95% CI, 0.72 to 0.95). There were fewer acute exacerbations in the azithromycin group than the placebo group regardless of the rate of acute exacerbations per patient-year (P=0.008). The number needed to treat to prevent one acute exacerbation of COPD was 2.86.

The median time to the first acute exacerbation of COPD was 266 days (95% CI, 227 to 313 days) in the azithromycin group and 174 days (95% CI, 143 to 215 days) in the placebo group (P<0.001). The hazard ratio of having an acute exacerbation of COPD per patient-year in the azithromycin group as compared with the placebo group was 0.73 (95% CI, 0.63 to 0.84; P<0.001).

Quality of life scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4; P=0.004).

There were no differences in serious adverse events between the study and control groups. An audiogram-confirmed hearing decrement occurred in 142 of the patients receiving azithromycin (25%), compared with 110 of those receiving placebo (20%) (P=0.04). But, researchers said, hearing improved with repeat testing regardless of whether the study drug was discontinued. This suggests that study criteria were too stringent and that the incidence of hearing decrements was overestimated in both groups, they concluded.

Patients receiving azithromycin were less likely to become colonized with respiratory pathogens but were more likely to become colonized with macrolide-resistant organisms. However, no evidence suggested this was related to exacerbations or pneumonia. There were no adverse cardiac effects from azithromycin, although researchers noted that patients were excluded if they had risk factors for prolongation of the QTc interval.

The researchers concluded, "Given the deleterious effects of acute exacerbations of COPD with respect to the risk of death, quality of life, loss of lung function, and cost of care, adding azithromycin to the treatment regimen of patients who have had an acute exacerbation of COPD within the previous year or who require supplemental oxygen is a valuable option."

However, patients should be screened for risk of QTc prolongation, hearing should be monitored, and it should be recognized that the long-term effects of this treatment on microbial resistance are not known, they cautioned.

Hypertension

Ambulatory blood pressure monitoring may be most cost-effective for hypertension diagnosis

Ambulatory measurement is the most cost-effective method of diagnosing high blood pressure, a new analysis concluded.

The Markov model-based analysis used a hypothetical primary care population age 40 or over with a screening blood pressure measurement over 140/90 mm Hg and an average risk factor prevalence. Researchers compared three strategies for definitively diagnosing hypertension: additional clinic measurements, home measurement, and ambulatory monitoring. The results were published online Aug. 24 by The Lancet.

Ambulatory monitoring was found to be the most cost-effective strategy, because it was cost-saving in all age and sex subgroups and it resulted in more quality-adjusted life-years for people over 50. The authors used a wide range of sensitivity analyses and found the results to be robust, except if home monitoring was considered to be as effective as ambulatory monitoring. Ambulatory monitoring costs more than the other methods, but the costs are counterbalanced by savings from better targeted treatment, the authors said.

The cost-effectiveness of ambulatory monitoring could be even greater than the study found because the model was based on generic drug costs and assumed no negative quality of life effects from a diagnosis of hypertension (in patients who both did and didn't actually have the condition). An accompanying comment noted that the model also assumed no benefit to hypertension treatment for people whose blood pressure was below 140/90 mm Hg.

The model also assumed a 5-year cycle of rescreening, and ambulatory monitoring would not be as cost-effective in younger patients if it were conducted annually, the study authors cautioned. Overall, however, they recommended that ambulatory monitoring be seriously considered for most people before the start of hypertension treatment.

Asleep blood pressure could present a novel target for CVD risk

Taking one or more blood pressure (BP) drugs at bedtime reduced asleep blood pressure and cardiovascular disease risk compared to taking all hypertension drugs upon awakening, a new study found.

Spanish researchers prospectively studied a consecutive series of 3,344 adult patients. They had been recruited from those referred to the hospital for ambulatory blood pressure monitoring (ABPM) mainly to confirm hypertension or to evaluate control in already treated patients. Inclusion criteria required patients to be normotensive, untreated hypertensive, or resistant to treatment. Results were published online Aug. 29 by the Journal of the American College of Cardiology.

Hypertension in untreated patients was defined as awake mean BP over 135/85 mm Hg and/or an asleep mean BP over 120/70 mm Hg. By these criteria, 734 patients were normotensive and 2,610 were hypertensive (776 with resistant hypertension).

Patients with untreated hypertension were randomly assigned to take medication either upon awakening or at bedtime. Participants with resistant hypertension were randomized to either exchanging one of their medications with a new one while taking all medications in the morning or shifting one BP drug to bedtime.

During the median follow-up period of 5.6 years, there were 331 cardiovascular events. These occurred among patients who were predominantly male; were older; and at baseline were likely to have type 2 diabetes, obstructive sleep apnea, metabolic syndrome, and/or abdominal obesity. The patient's mean asleep BP was the most significant predictor of major cardiovascular disease (CVD) events, researchers reported. The reduced hazard ratio (HR) associated with each 5-mm Hg decrease in mean asleep systolic pressure during follow-up was significant for patients with normal (HR, 0.81; 95% CI, 0.68 to 0.95; P<0.005) or elevated BP (HR, 0.84; 95% CI, 0.79 to 0.89; P<0.001).

The researchers wrote, "All together, these results not only corroborate that the asleep BP mean is the most significant prognostic marker of CVD morbidity and mortality, as previously suggested, but also document for the first time that decreasing asleep BP mean significantly reduces CVD risk."

An editorial noted that a strong case has been made to move at least some part of the antihypertensive regimen to bedtime as a default standard, but also cautioned that the safety of nighttime drug administration must be established. Nocturnal hypotension could result in cerebral and myocardial ischemia.

Still, the editorialists wrote, "The mere suggestion that CV event rates in patients with hypertension can be reduced by more than 50% with a zero-cost strategy of giving existing medications at bedtime rather than in the morning is nothing short of revolutionary."

Prescribing

Long-term medications often discontinued during hospitalization

Patients taking medication for chronic diseases risk those prescriptions being discontinued when they are hospitalized, especially if they are admitted to an intensive care unit (ICU), a new study found.

The population-based cohort study used data from hospitalizations and outpatient prescriptions in Canada between 1997 and 2009. It included almost 400,000 patients age 66 or older who were taking a drug from at least one of these medication categories: statins, antiplatelet/anticoagulants, levothyroxine, respiratory inhalers and gastric acid-suppressing drugs. About 188,000 of the patients were admitted to the hospital during the study and the other patients served as controls.

The study found that all five classes of drugs were more likely to be discontinued in the hospitalized patients. The increased risk of discontinuation was the highest for those taking antiplatelet/anticoagulants; those drugs were discontinued in 19.4% of hospitalized patients versus 11.8% of controls (adjusted odds ratio [AOR], 1.86). At the other end of the range was levothyroxine (discontinued in 12.3% of hospitalized patients vs. 11% of controls; AOR, 1.18). Admission to the ICU was associated with an even greater risk of discontinuation for four out of the five drug categories; for example, 22.8% of ICU patients had their antiplatelet/anticoagulants discontinued.

Researchers also followed the patients for one year and found that discontinuation of statins or antiplatelet/anticoagulants were associated with an increased risk of a composite outcome of death, emergency department visit or emergent hospitalization (AOR, 1.07 for statins and 1.10 for antiplatelet/anticoagulants). The results appeared in the Aug. 24/31 Journal of the American Medical Association.

The studied medications were chosen because their discontinuation has been associated with adverse events, the study authors said, and thus the findings highlight both the prevalence of unintentional medication discontinuation and the potential harms that could result. They acknowledged that the study was not able to definitively determine whether medications may have been discontinued intentionally but steps were taken to minimize such confounding, including exclusion of patients with diagnoses that would contraindicate the drugs.

The authors suggested strategies to correct the problem, including formal medication reconciliation at ICU discharge, better communication among clinicians and system-based methods to ensure continuity (which could range from simple forms to customized computer systems). However, the focus should not be solely within the hospital, an accompanying editorial pointed out. The editorialists called for "more powerful solutions," including comprehensive electronic health records available to all clinicians in a health care system and incentives for communication across care sites.

FDA update

Daily citalopram dose shouldn't be higher than 40 mg

The antidepressant citalopram hydrobromide (Celexa) should no longer be used at doses greater than 40 mg/d, according to a new warning from the FDA.

Doses over 40 mg can cause prolongation of the QT interval and lead to an abnormal heart rhythm (including torsade de pointes), an FDA press release said. Trials of the drug have not shown a benefit in the treatment of depression at doses higher than 40 mg/d, but the citalopram drug label previously stated that certain patients may require a dose of 60 mg/d. The label has been revised to include the new dosage and usage recommendations.

An even lower dose, 20 mg/d, is the maximum recommended dose for patients who have hepatic impairment, are older than 60 years of age, are CYP 2C19 poor metabolizers, or are taking concomitant cimetidine (Tagamet), because these factors lead to increased blood levels of citalopram, increasing the risk of QT interval prolongation and torsade de pointes.

The FDA also advised clinicians that citalopram should not be used in patients with congenital long QT syndrome. In patients who do take the drug, hypokalemia and hypomagnesemia should be corrected before administering citalopram. Electrolytes should be monitored as clinically indicated. Physicians should consider more frequent electrocardiogram monitoring in patients who have congestive heart failure, those who have bradyarrhythmias, or those who take concomitant medications that prolong the QT interval.

CMS update

Applications now being accepted for bundled payment initiative

The Centers for Medicare and Medicaid Services is currently soliciting applications for the Bundled Payments for Care Improvement Initiative.

The initiative will work to align all of the payments for a single episode (e.g., a heart bypass or hip replacement) to encourage improved coordination of care. The hope is that this will lead to both improved quality of care and cost savings for Medicare, and participating clinicians may be able to share in any savings that result.

Interested parties must submit a letter of intent by Sept. 22 for the first stage of the program, or by Nov. 4 for subsequent stages. The program is being run by the Center for Medicare and Medicaid Innovation, which was created last year as part of the Affordable Care Act. More information is available on the CMS website.

Education

Correctional health care conference to be held in October

The National Commission on Correctional Health Care will hold its national conference Oct. 15-19, 2011, in Baltimore.

The conference will explore options for effective treatment, education, prevention and research. Preconference seminars will address fundamental topics such as commission standards for jails, prisons, and juvenile facilities. More than 100 presentations on a broad range of subjects will be provided in the areas of medical care, nursing, cost containment, legal issues, mental health services and much more. The conference also will be the test site for the Certified Correctional Health Professional exam. ACP is a supporting organization of the National Commission on Correctional Health Care. For more complete information, visit the commission website, call 773-880-1460, or send an e-mail.

Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.

E‑mail all entries to acpinternist@acponline.org. ACP staff will choose finalists and post them online for an online vote by readers. The winner will appear in an upcoming edition.

MKSAP Answer and Critique

The correct answer is A) Collapsing focal segmental glomerulosclerosis. This item is available to MKSAP 15 subscribers as item 4 in the Nephrology section. More information about MKSAP 15 is available online.

This patient most likely has HIV-associated nephropathy (HIVAN) caused by collapsing focal segmental glomerulosclerosis (FSGS). Collapsing FSGS is the most common kidney disease associated with HIV infection and predominantly affects black patients. HIVAN is classically associated with a low CD4 cell count and high HIV RNA viral load but may manifest differently in patients whose HIV infection is well controlled with highly active antiretroviral therapy (HAART) or who have an acute retroviral syndrome. Collapsing FSGS is characterized by hypoalbuminemia, edema, heavy proteinuria, and minimal erythrocytes and leukocytes in the urine. Most patients have a normal blood pressure.

HAART is considered the treatment of choice in patients with HIVAN, and protease inhibitor–based HAART regimens have been shown to reduce the progression of kidney disease in this setting; adding corticosteroids to this therapy may provide further benefit. In addition, treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker helps to decrease urine protein excretion.

Postinfectious glomerulonephritis and IgA nephropathy are possible kidney complications of HIV infection. Postinfectious glomerulonephritis can potentially develop after numerous bacterial infections, which frequently occur in patients with HIV infection. IgA nephropathy may be the result of IgA interaction with HIV antigens but would manifest as minimal proteinuria and an active urine sediment, which is not compatible with this patient's presentation.

Membranous nephropathy can cause the nephrotic syndrome in patients with HIV infection. Membranous nephropathy is most commonly associated with HIV infection–related complications such as hepatitis B or C virus infection or syphilis and may be associated with renal vein thrombosis, which are absent in this patient. This condition also is associated with systemic lupus erythematosus and the use of certain drugs, but these circumstances are unlikely in a patient who takes no medications and has a negative antinuclear antibody assay.

Key Point

The most common cause of HIV-associated nephropathy is collapsing focal segmental glomerulosclerosis, which is characterized by massive proteinuria.

Test yourself

A 54-year-old woman is evaluated for shortness of breath of 3 months' duration and a 4.5-kg (10-lb) weight loss over the preceding 2 months. She has a 35-pack-year smoking history. Following a physical exam and further testing, what is the most appropriate treatment?

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